| Title: |
Global multi-ancestry genetic study elucidates genes and biological pathways associated with thyroid cancer and benign thyroid diseases |
| Authors: |
White, Samantha L.; Brasher, Maizy S.; Pattee, Jack; Zhou, Wei; Chapman, Sinéad; Jee, Yon Ho; Bell, Caitlin C.; Jamil, Taylor L.; Barrio, Martin; Hirbo, Jibril; Cox, Nancy J.; Straub, Peter; Namba, Shinichi; Bertucci-Richter, Emily; Guare, Lindsay; EdrisMohammed, Ahmed; Morris, Sam; Mulford, Ashley J.; Zhang, Haoyu; Fennessy, Brian; Tobin, Martin D.; Chen, Jing; Williams, Alexander T.; John, Catherine; van Heel, David A.; Mathur, Rohini; Finer, Sarah; Moksnes, Marta Riise; Brumpton, Ben; Åsvold, Bjørn Olav; Peculis, Raitis; Rovite, Vita; Konrade, Ilze; Wang, Ying; Crooks, Kristy; Chavan, Sameer; Fisher, Matthew J.; Rafaels, Nicholas; Lin, Meng; Shortt, Jonathan; Sanders, Alan R.; Whiteman, David; MacGregor, Stuart; Medland, Sarah; Thorsteinsdóttir, Unnur; Stefánsson, Kári; Karaderi, Tugce; Egan, Kathleen M.; Bocklage, Therese; McCrary, Hilary C.; Riedlingeer, Greg; Salhia, Bodour; Shriver, Craig; Phan, Minh D.; Farlow, Janice L.; Edge, Stephen; Kaur, Varinder; Churchman, Michelle; Rounbehler, Robert J.; Brock, Pamela L.; Ringel, Matthew D.; Pividori, Milton; Schweppe, Rebecca; Raeburn, Christopher D.; Walters, Robin; Chen, Zhengming; Li, Liming; Matsuda, Koichi; Okada, Yukinori; Zoellner, Sebastian; Verma, Anurag; Preuss, Michael; Kenny, Eimear; Hendricks, Audrey; Fishbein, Lauren; Kraft, Peter; Daly, Mark; Neale, Benjamin; Biobank at the Colorado Center for Personalized Medicine; Genes & Health Research Team; BioBank Japan Project; Martin, Alicia; Cole, Joanne B.; Haugen, Bryan R.; Gignoux, Christopher R.; Pozdeyev, Nikita |
| Contributors: |
Otolaryngology -- Head and Neck Surgery, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
medRxiv |
| Publication Year: |
2025 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
Thyroid diseases; Genetic correlation; Genetic predisposition; Thyroid cancer risk |
| Description: |
Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer, benign nodular goiter, Graves' disease, lymphocytic thyroiditis, and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 235 known and 501 novel independent variants significantly linked to thyroid diseases. We discovered genetic correlations between thyroid cancer, benign nodular goiter, and autoimmune thyroid diseases (r 2 =0.21-0.97). Telomere maintenance genes contribute to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair, and DNA damage response genes are predominantly associated with thyroid cancer. We proposed a paradigm explaining genetic predisposition to benign and malignant thyroid nodules. We evaluated thyroid cancer polygenic risk scores (PRS) for clinical applications in thyroid cancer diagnosis. We found PRS associations with thyroid cancer risk features: multifocality, lymph node metastases, and extranodal extension. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://hdl.handle.net/1805/49505 |
| Availability: |
https://hdl.handle.net/1805/49505 |
| Rights: |
Attribution-NonCommercial 4.0 International ; https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.749D31A7 |
| Database: |
BASE |